A Comprehensive Overview of Recent Advances in Epigenetics in Pediatric Acute Lymphoblastic Leukemia

SIMPLE SUMMARY: Acute lymphoblastic leukemia (ALL) is the most common cancer among pediatric patients. Thanks to the introduction of revolutionary treatment methods and advances in our understanding of the pathogenesis of this disease over the last few decades, survival rates of childhood ALL have increased from less than 10% in the 1960s to almost 90% currently in developed countries. However, there is still a need for further improvement. The latest findings in the field of epigenetics and acute lymphoblastic leukemia show promising potential for the treatment and diagnostics of this disease. The aim of this review is to summarize our current knowledge, according to recent findings, on epigenetics in childhood acute lymphoblastic leukemia, including specific epigenetic alterations in ALL, their potential use as biomarkers for classification, predicting relapse and disease progression, as well as them being targets for novel therapeutic strategies. ABSTRACT: Recent years have brought a novel insight into our understanding of childhood acute lymphoblastic leukemia (ALL), along with several breakthrough treatment methods. However, multiple aspects of mechanisms behind this disease remain to be elucidated. Evidence suggests that leukemogenesis in ALL is widely influenced by epigenetic modifications. These changes include: DNA hypermethylation, histone modification and miRNA alteration. DNA hypermethylation in promoter regions, which leads to silencing of tumor suppressor genes, is a common epigenetic alteration in ALL. Histone modifications are mainly caused by an increased expression of histone deacetylases. A dysregulation of miRNA results in changes in the expression of their target genes. To date, several hundred genes were identified as suppressed by epigenetic mechanisms in ALL. What is promising is that epigenetic alterations in ALL may be used as potential biomarkers for classification of subtypes, predicting relapse and disease progression and assessing minimal residual disease. Furthermore, since epigenetic lesions are potentially reversible, an activation of epigenetically silenced genes with the use of hypomethylating agents or histone deacetylase inhibitors may be utilized as a therapeutic strategy for ALL. The following review summarizes our current knowledge about epigenetic modifications in ALL and describes potential uses of epigenetics in the clinical management of this disease.